tbuckley/cabot-search huggingface dataset:
Sleeve Sign and Inverse Gottron’s Papules in Anti-MDA5 Dermatomyositis
Authors: Wei-Yao Wang, Shih-Tsung Cheng
Journal: New England Journal of Medicine (2023)

A 46-year-old woman presented with shortness of breath, dry cough, and painful rash on the upper arms. Examination was notable for erythematous lesions on the lateral upper arms and ventral surfaces of the hands.
P06.11.B NEUROTOXICITY AND MANAGEMENT OF PRIMARY AND SECONDARY CNS LYMPHOMA AFTER ADOPTIVE IMMUNOTHERAPY WITH CD19-DIRECTED CAR T-CELLS
Authors: P Karschnia, I C Arrillaga-Romany, A Eichler, D A Forst, E Gerstner, J T Jordan, I Ly, S R Plotkin, N Wang, M Martinez-Lage, S F Winter, J Tonn, K Rejeski, L von Baumgarten, D P Cahill, B V Nahed, G M Shankar, J S Abramson, J A Barnes, A El-Jawahri, E P Hochberg, P Johnson, J D Soumerai, R W Takvorian, Y Chen, M J Frigault, J Dietrich
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Chimeric antigen receptor (CAR) T-cells targeting CD19 have been established as a leading engineered T-cell therapy for systemic B-cell lymphomas; however, data for patients with CNS involvement are limited. Whether CAR T-cells represent a viable therapeutic avenue for such patients remains therefore unclear. MATERIAL AND METHODS We retrospectively searched our institutional database for patients with primary and secondary CNS lymphoma who were treated with CD19-directed CAR T-cells for active CNS disease. Clinical data, CNS-specific toxicities, imaging findings, and outcome were analyzed. RESULTS We identified 45 consecutive CAR T-cell transfusions for active CNS lymphoma at the Massachusetts General Hospital over a five-year period. This cohort includes 17 patients with primary CNS lymphoma (PCNSL; one patient with two CAR T-cell transfusions) and 27 patients with secondary CNS lymphoma (SCNSL). Mild neurotoxicity (grade 1-2) was observed after 19/45 transfusions (42.2%) and severe neurotoxicity (grade 3-4) after 7/45 transfusions (15.6%). A larger increase in C-reactive protein (CRP) levels and higher rates of neurotoxicity were detected in SCNSL. Early fever and baseline C-reactive protein levels predicted neurotoxicity occurrence. CNS response was seen in 31 cases (68.9%), including a complete response of CNS disease in 18 cases (40.0%) which lasted for a median of 11.4 ± 4.5 months. Dexamethasone dose at time of lymphodepletion (but not at or after CAR T-cell transfusion) was associated with an increased risk for CNS progression (HR per mg/d: 1.16, p = 0.031). If bridging therapy was warranted, the use of Ibrutinib translated into favourable CNS-progression free survival (5 versus 1 month, HR 0.28, CI 0.1-0.7; p = 0.010). CONCLUSION CD19-directed CAR T-cells exhibit promising anti-tumor effects and a favourable safety profile in patients with CNS lymphoma. Further evaluation on the role of bridging regimens and corticosteroids is urgently warranted.
JS09.6.A ASSESSMENT OF RESPONSE TO REGORAFENIB IN RECURRENT GLIOMA PATIENTS USING FET PET AND MRI INCLUDING ADC VALUES
Authors: J Werner, P Lohmann, C Kabbasch, M M Wollring, C Tscherpel, G Stoffels, R Goldbrunner, K Langen, G R Fink, N Galldiks
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND The phase 2 REGOMA trial suggested that glioblastoma patients treated with the multikinase inhibitor regorafenib at first progression have significantly longer overall survival than patients treated with lomustine. Here, we evaluated the value of O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET and MRI for the evaluation of response to regorafenib in recurrent glioma patients. MATERIAL AND METHODS Twenty patients (age range, 30-72 years) with CNS WHO grade 3 or 4 gliomas (glioblastoma, 85%) at recurrence were treated according to the REGOMA trial with regorafenib at 160 mg/d for the first three weeks of each 4-week cycle, with individual dose adjustment according to toxicity. FET PET and MRI were performed at baseline and follow-up after the second cycle. Static FET PET parameters comprised tumor-to-brain ratios (TBR) and metabolic tumor volumes (MTV). Parameters derived from dynamic FET PET acquisition were time-to-peak and slope. MRI response assessment was based on RANO criteria. Additionally, mean and minimum apparent diffusion coefficients (ADC) were obtained from diffusion-weighted MRI. FET PET parameters and ADC thresholds were defined using ROC analyses to predict an overall survival of ≥ 6 months. The predictive values of FET PET parameters, ADC values, and RANO criteria were subsequently evaluated using univariate and multivariate survival estimates. RESULTS Patients received a median of three regorafenib cycles (range, 2-10 cycles). After treatment initiation, the median follow-up was 8.6 months (range, 3.2-27.3 months). The median number of previous treatment lines was two (range, 1-4 lines). At the time of data analysis, 17 patients (85%) had died. After two cycles of regorafenib, a regorafenib-induced reduction of mean TBR values by ≥ 10% predicted a longer overall survival (9.9 vs. 5.3 months; P=0.023). Interestingly, absolute mean TBR values ≤ 2.0 at follow-up were prognostic and associated with longer OS (10.6 vs. 4.5 months; P=0.007). In contrast, MTV, dynamic PET parameters, RANO criteria, and ADC values were not predictive for response or prognostic (all P&amp;gt;0.05). Multivariate survival analyses revealed that relative mean TBR changes were most potent in predicting response to regorafenib (P=0.038; HR, 0.246) and absolute mean TBR values for prognostication (P&amp;lt;0.001; HR, 0.005). CONCLUSION Data suggest that FET PET parameters are clinically valuable for identifying responders to regorafenib early after treatment initiation and helpful for prognostication. MRI parameters, including ADC values, do not appear to add valuable information in this context.
P09.01.A IMPACT OF TIMING OF ANTISEIZURE MEDICATION WITHDRAWAL ON SEIZURE RECURRENCE IN GLIOMA PATIENTS: A RETROSPECTIVE OBSERVATIONAL STUDY
Authors: P B van der Meer, L Dirven, M Fiocco, M J Vos, M Kerkhof, M C Kouwenhoven, M J van den Bent, M J B Taphoorn, J A F Koekkoek
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Withdrawal of antiseizure medication treatment (ASM) can be considered after completion of antitumour treatment in glioma patients who no longer suffer from seizures. We compared the risk of recurrent seizures after ASM withdrawal between patients with short-term, medium-term versus long-term seizure freedom after antitumour treatment. MATERIAL AND METHODS In this retrospective observational study, the primary outcome was time to recurrent seizure, from the starting date of no ASM treatment up to 36 months follow-up. Cox proportional hazards models were used to study the effect of risk factors on time to recurrent seizure. Stratification was done with information known at baseline. Short-term seizure freedom was defined as ≥3 months, but &amp;lt;12 months; medium-term as 12-24 months; and long-term as ≥24 months seizure freedom from the date of last antitumour treatment. RESULTS This study comprised of 109 patients; 31% (34/109) were in the short-term, 29% (32/109) in the medium-term, and 39% (43/109) in the long-term group. A recurrent seizure was experienced by 44% (15/34) of the patients in the short-term, 31% (10/32) in the medium-term, and 44% (19/43) in the long-term group. Seizure recurrence risk was similar between patients in the short-term group as compared to the medium-term (cause-specific adjusted hazard ratio [aHR]=0.65 [95%CI=0.29-1.46]) and long-term group (cause-specific aHR=1.04 [95%CI=0.52-2.09]). CONCLUSION Seizure recurrence risk is relatively similar between patients with short-term, medium-term, and long-term seizure freedom after completion of antitumour treatment.
P11.38.A CYSTIC VESTIBULAR SCHWANNOMA - A SUBGROUP ANALYSIS FROM A COMPARATIVE STUDY BETWEEN RADIOSURGERY AND MICROSURGERY
Authors: S Wang, G Naros, A van Eck, G Horstmann, M Tatagiba
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Some vestibular schwannoma (VS), show cystic morphology. It is known that these cystic vestibular schwannomas (cVS) bear different surgical risk profile compared to non-cystic VS (ncVS) in surgical treatment. This study aims to analyze the management of cVS compared to ncVS in a dual center study of surgically (SURG) and radiosurgically (SRS) treated VS patients. MATERIAL AND METHODS This is a retrospective multi-center cohort study. Data was retrospectively collected from two large centers involved in the treatment of vestibular schwannomas for patients between 2005 und 2011 to enable long-term follow-up (FU). Tumor size was classified by Koos Classification. Previously treated VS and VS associated with Neurofibromatosis were excluded. Clinical state was reported by House and Brackmann (H&amp;B) and Gardner-Robertson (G&amp;R) scale (with H&amp;B and G&amp;R 1-2 considered as good outcome), and Recurrence-free-survival (RFS) was assessed radiographically by contrast-enhanced MR imaging. Data on VS-associated symptoms like trigeminal affection, tinnitus, and vertigo/imbalance were also collected. RESULTS The study population included N=901 patients, who were treated in both centers. N=559 (62%) patients were treated by SRS, and N=342 (38%) patients by SURGERY. N=55 (6%) of all patients showed cystic MR-morphology. These were more often treated by SURG (N=31/55, 58%) compared to ncVS (N=311/845, 37%) (p=0.002). Patients with cVS were indifferent in mean age compared to ncVS. The rate of women was higher in cVS (64%), compared to ncVS (55%) (p=0.001). The overall incidence of recurrence was 16% in cVS (8% in ncVS). Tumor control was worse in cVS treated by SRS (N=6/24, 25%) compared to SURGERY (N=3/32, 9%). When surgically treated, gross total resection (GTR) was achieved in 87% in cVS, whereas this rate was higher in non-cystic VS at 96% (p=0.001). The number of patients N=5/32 (16%) with postoperative relevant facial palsy (HB&amp;gt;2) was significantly higher in cVS (ncVS: N=28/310; 9%). CONCLUSION Tumor control in cVS is significantly worse in SRS compared to SURG and SRS-treated ncVS. However, when cVS is treated surgically, the rate of GTR is lower and the number of patients with relevant postoperative facial palsy higher compared to ncVS. Cystic morphology in VS poses a challenge in management (both SRS and SURG) compared to non-cystic tumors. Treatmend decision and patients' consultation should contemplate and address negative prognostic factor of cystic morphology in VS.
P08.11.A PREDICTIVE SOCIAL FACTORS ASSOCIATED TO PLACE OF DEATH IN MALIGNANT GLIOMAS
Authors: D Benincasa, V Villani, S Focarelli, A Tanzilli, F Cardone, A Biscu, D Alò, S Di Felice, A Pace
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Malignant gliomas (MG) are tumors affecting central nervous system (CNS) with a poor prognosis. Fast neurological decline (motor, cognitive and behavioural) causes high burden for patients and caregivers and requires specific setting of care (especially palliative care) helping patients to preserve their autonomy and assuring, in the end of life phase, the best care represented by dying at home with dignity that is considered in the literature an indicator of good quality of care in cancer patients. MATERIAL AND METHODS The home care program for MG utilized in our Institution is aimed to offer palliative and supportive care during all the trajectory of disease and to facilitate death at home. To identify possible factors related with place of death, we’ve retrospectively investigated social and health data to discover possible factors associated with dying at home in MG patients. Every patient and caregiver/family were analyzed for many factors including sex, work, family relation, presence or absence of caregiver/family, presence of children. RESULTS From January 2016 to December 2020, we’ve assisted at home 263 MG patients and collected complete data in 257 patients (6 patients was lost in follow-up). 174 (68%) of them were affected by Glioblastoma Multiforme (GBM) and 83 (32%) were affected by grade 3 anaplastic gliomas; 155 patients (61%) were male and 102 (39%) female. 137 patients (54%) died at home, 88 patients (34%) died in hospice and 32 patients (12%) died in hospital. Male caregivers assisted 178 MG patients of which 141 was male patients (79%); female caregivers assisted 79 MG patients of which 65 was female patients (82%) (p&amp;lt;0.001); presence of social network (family or other type) influenced positively place of death: MG patients who has social network died frequently at home respect on MG patients who didn’t have social network that died frequently in hospital or hospice (p&amp;lt;0.001). No differences were found between age, sex (patient and caregiver), presence of minor children, education level, work, marital status and place of death. CONCLUSION In this cohort of MG patients followed with a palliative home care service, place of death and dying with dignity is influenced by presence of social network and reliable caregiver. The evaluation social data in addition to clinical data is an important factor in order to plan timely the end of life phase and the decisions about possible place of death.
P02.18.B INTEGRATIVE OMICS ANALYSIS OF IDH1 MUTANT GLIOMA PATIENTS REVEALS ALTERATIONS IN BUTYRATE METABOLISM
Authors: S Fritah, A Cano-Galiano, R Toth, A Hau, E Martinez-Garcia, M Allega, D Sumpton, F Fack, M Dieterle, M Adiamah, M Gobin, N Nicot, A Muller, T Kaoma, A Lesur, M Mittelbronn, E van Dyck, M Prasad Bekal, Y Esquenazi, K Hiller, P Sakariassen, H Miletic, G Dittmar, P Nazarov, S Tardito, M Lund-Johansen, R Bjerkvig, A Golebiewska, S Niclou
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Mutations in isocitrate dehydrogenase (IDH) 1 or 2 define glioma classification and determine the biology of these tumors. Although IDH is an essential enzyme in the cellular metabolism, powerful genome-wide analyses focus mostly at the genetic and epigenetic levels, while differences between distinct glioma entities at the proteomics, metabolomics, and functional levels are still poorly understood. Here, we provide an integrative multi-omics analysis of glioma patients to reveal metabolomic vulnerabilities of gliomas stratified by IDH mutation. MATERIAL AND METHODS We performed a multi-omics analysis of two cohorts of glioma patients (n=28) stratified based on IDH mutation status. Molecular assessment included LC-MS analysis, EPIC DNA methylation arrays, RNA-seq/HTA array-based transcriptomics and label-free quantitative proteomics. In 13 patients 13C-glucose was injected prior to surgery and tumor and adjacent brain tissue was collected. Gut microbial profiling using 16S ribosomal RNA (rRNA) sequencing was performed in a separate cohort of 128 glioma patients and 24 healthy individuals. Additional validation was performed in isogenic glioma stem-like cultures with CRISPR knock-in of IDH mutation. RESULTS We show that several molecular layers collectively contribute to biological differences between IDH mutant and wild-type gliomas, with strongest differences observed at the DNA methylation level. IDH mutant gliomas present specific molecular features linked to tumor metabolism. We confirm previous findings on 2-HG, cysteine and de novo glutathione synthesis pathways, which are specifically altered in IDH mutant gliomas. We further identify butyrate metabolism as a novel pathway highly active in IDH mutant gliomas. Butyrate is a bacterial metabolite with multiple systemic effects that is normally synthesized in the gut. This is supported by our gut microbiota metagenomics analysis of glioma patients. Yet the detection of enzymes associated with butyrate metabolism in tumor tissue and cell lines suggests a differential/enhanced metabolic rewiring of the butyrate signaling in IDH mutant gliomas CONCLUSION Our data shows the importance of multiple molecular layers in shaping specific features of IDH mutant gliomas. We unravel an activated butyrate metabolism in IDH mutant gliomas that may underly a novel gut-brain axis in glioma patients.
P11.72.A INTRACRANIAL CONTROL OF BRAIN METASTASES IN PATIENTS TREATED WITH RADIOTHERAPY PLUS CHEMOTHERAPY, IMMUNOTHERAPY, TARGETED THERAPY AND IMMUNOCHEMOTHERAPY OR TARGETED THERAPY WITH CHEMOTHERAPY
Authors: A Sulejmani, G Rinkel, N Etminan, S Brehmer
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Brain metastases (BM) are the most common intracranial malignancy. For many years, patients with BM were excluded from clinical trials of systemic cancer therapies based on their presumed bad prognosis, which results in a therapeutic nihilism as soon a BM is diagnosed. With the development of immunotherapies and targeted therapies as systemic cancer therapy, we questioned if there is a difference in intracranial response, regardless of the indicated radiotherapy (RT) for the BM. MATERIAL AND METHODS 67 patients older than 18 years, with multiple BM treated between December 2016 and October 2021, with in total 237 metastases were analyzed. The volume of each metastasis on MRI was calculated at the time of appearance and every 3 months thereafter. The primary outcome was intracranial control according to RANO-BM at 6 months. Because of missing data (MRI at 6 months), 92 metastases had to be excluded, leaving 145 for the analysis. Patients were divided into groups (RT+chemotherapy - CT-group, RT+immunotherapy/targeted therapy - IT/TT-group, RT+chemo-immunotherapy/targeted therapy - CT+IT/TT-group). The second outcome measure was time to progression of metastases; for this outcome 183 metastases could be analyzed. For statistical analysis chi-square test and Tarone-Ware test were performed. RESULTS In the CT-group (n=40)10% (n=4) had a progressive disease (PD), 33% (n=13) had a partial response (PR), 57 % (n=23) complete response (CR), and no one stable disease (SD). In the CT+IT/TT-group (n=28) 14% (n=4) had PD, 11% (n=3) SD, 11% (n=3) PR and 64% (n=18) CR. In the IT/TT-group (n=78) 14% (n=11) had PD, 4% (n=3) SD, 26% (n=20) PR and 56% (n=44) CR. The p values for difference in intracranial control were between CT-group/IT/TT-group 0,81 and between CT-group/CT+IT/TT-group 0,58. Patients in the IT/TT-group had a better outcome if a targetable mutation was present (p=0,005). The median time to progression (days) was 474 ± 30 for the CT-group; 581 ± 50 for the IT/TT- group and 360 ± 35 for the CT+IT/TT-group. Tarone-Ware test showed a trend in the progression distributions between the 3 groups favoring the IT/TT-group p= 0,082. CONCLUSION Intracranial response could be achieved in all analyzed subgroups without statistically significant difference. Against the background of this data, the therapeutic nihilism due to the presumed bad prognosis is not justified. A subgroup analysis of the IT /TT group showed a significantly better outcome for patients who had a matching gene. Patients who received immunotherapy or targeted therapies showed a trend towards later progression than chemotherapy or combination therapy. Larger patient cohorts should be investigated to see if this trend could be confirmed.
P11.77.B PREDICTING SURVIVAL IN GLIOBLASTOMA PATIENTS WHO DON’T UNDERGO NEUROSURGERY
Authors: Y de Haan, M de Roover, D Duijnkerke, N Colmer, M Smits, C M F Dirven, A J P E Vincent
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Patients with glioblastoma have poor overall survival (OS), even with surgical treatment and adjuvant therapy. However, up to a quarter of patients with presumed glioblastoma does not receive any form of treatment and not much is known in the literature about this population. Their OS is estimated to be around 1.2 months. Generally, patients with presumed glioblastoma that don’t receive any form of treatment do so either because of their poor physical condition or because of their own preference. Receiving a terminal diagnosis comes with psychological and existential distress and providing a more personalized prognosis of survival may be beneficial in acceptance and end-of-life decision-making. We aimed to evaluate overall survival in a large cohort and analyze which clinical and radiological factors predict overall survival in this population. METHODS Patients in this retrospective cohort were included in a tertiary hospital in the Netherlands. Patients were eligible if they were aged above 18 years old and didn’t receive any treatment for their presumed glioblastoma. We used a log-rank test to analyze the differences in the survival between the groups are not fit enough for surgery and the group that prefers to not undergo any treatment. We performed Cox regression to analyze the predictive value of clinical and radiological factors on survival. RESULTS Between January 1st, 2010 and 31st December 2022 212 patients were included. The median OS of the entire cohort was 2.68 months. In the group with poor physical condition as reason for not undergoing surgery, the median OS was 1.92 months versus an OS of 2.73 months in the group that didn’t want to undergo treatment (p=0.0174). In univariate Cox regression analysis, location in the right hemisphere, not receiving any treatment because of poor physical condition, tumor crossing the midline, Karnofsky Performance Scale lower than 70, a multifocal lesion in the contralateral hemisphere and NIHSS of 5 or higher had a statistically significant increased Hazard Ratio for OS.Additional analysis of the statistical significance in a multivariable model is still ongoing. CONCLUSION This large retrospective cohort of patients with presumed glioblastoma that don’t receive any treatment provides more robust information about expected median overall survival and gives physicians better tools in conversations about end-of life care based on factors that influence survival.